Characterization of native FGF23 protein and mutant forms causing autosomal dominant hypophosphatemic rickets and familial tumoral calcinosis [Elektronische Ressource] / vorgelegt von Anna Benet Pagès

Characterization of native FGF23 protein and mutant forms causing autosomal dominant hypophosphatemic rickets and familial tumoral calcinosis Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften (Dr. rer. nat.) der Fakultät für Biologie der Ludwig-Maximilians-Universität München vorgelegt von Anna Benet Pagès April 2005 eingereicht am: 09. Juni 2005 1. Gutachter: Prof. Dr. Thomas Cremer 2. Dr. Heinrich Leonhardt Sondergutachter: PD Dr. Tim-Matthias Strom Tag der mündlichen Prüfung: 23. Februar 2006 Table of contents TABLE OF CONTENTS TABLE OF CONTENTS …………………………………………………………….. 1 ABREVIATIONS ……………………………………………………………………. 5 SUMMARY ………………………………………………………………………….. 8 A. INTRODUCTION 1. PHOSPHATE HOMEOSTASIS …………………………………………….... 10 1.1 Phosphorus ……………………………………………………..………... 10 1.2 Phosphate transport ……………………………………………………… 11 1.3 Cellular mechanisms of renal phosphate transport .……………………... 12 1.4 Hormonal regulation ..…………………………………………………… 12 2. DISORDERS OF PHOSPHATE METABOLISM: Hypophosphatemias …….. 14 2.1 X-linked hypophosphatemia …………………………………………….. 15 2.1.1 Hyp and Gy mice models ……………………………………….… 16 2.1.2 Mutations in the PHEX gene cause XLH …………………………. 17 2.1.3 The PHEX protein ………………………………………………… 17 2.1.4 Relevance of PHEX in the pathophysiology of XLH ……………... 18 2.